A 19-year-old man is brought by his roommate to the emergency department for evaluation of confusion and disorganized behavior. The roommate states that he returned home from an afternoon outing to find the patient yelling about “eagles flying around the room” and trying to lift up his car. He is worried that the patient may have “taken something.” Past medical history is noncontributory. The patient is severely combative and uncoordinated in the exam room. Physical examination is significant for tachycardia, diaphoresis, ataxia, and vertical nystagmus.
Which of the following describes the primary mechanism of action of the most likely substance taken by the patient?
B) Antagonism of the NMDA receptor
This patient likely ingested phencyclidine (PCP), an NMDA receptor antagonist and dissociative anesthetic. PCP intoxication results in severe combativeness, sympathetic overactivity (diaphoresis, tachycardia), disorganized behavior, ataxia, dissociation, perceived superhuman strength, and increased pain tolerance. Multidirectional nystagmus is a hallmark finding.
Answer choice A: Allosteric activation of the GABAA receptor, is incorrect. This is the mechanism by which benzodiazepines, barbiturates, and alcohol exert their effects. These substances are depressants and are unlikely to present with the sympathetic overactivity found in this patient.
Answer choice C: Increased synaptic levels of serotonin, is incorrect. This is a mechanism by which 3,4-Methylenedioxymethamphetamine (MDMA; also known as ecstasy) exerts its effects. MDMA is a hallucinogenic stimulant which causes disinhibited euphoria, bruxism (teeth grinding), and increased sociability, empathy, and sexual desire. It can also cause life threatening hyperthermia and/or hyponatremia.
Answer choice D: Partial agonism at nicotinic acetylcholine receptors, is incorrect. This describes the mechanism of varenicline, a cholinomimetic used for smoking cessation. Overuse of varenicline can result in nausea, insomnia, and vivid dreams.
Answer choice E: Partial agonism at μ-opioid receptors, is incorrect. This describes the mechanism of buprenorphine, which is a central nervous system depressant used to attenuate opioid withdrawal symptoms.
Key Learning Point
Phencyclidine (PCP) exerts its effects through NMDA receptor antagonism. Intoxication with PCP can present with severe combativeness, sympathetic overactivity, ataxia, dissociation. Multidirectional nystagmus is a hallmark finding.
